374779-45-0Relevant articles and documents
Isomorphism, disorder, and hydration in the crystal structures of racemic and single-enantiomer carvedilol phosphate
Vogt, Frederick G.,Copley, Royston C. B.,Mueller, Ronald L.,Spoors, Grant P.,Cacchio, Thomas N.,Carlton, Robert A.,Katrincic, Lee M.,Kennady, James M.,Parsons, Simon,Chetina, Olga V.
, p. 2713 - 2733 (2010)
Understanding the crystalline structure of racemic carvedilol phosphate hemihydrate presents several challenges that were overcome using a combination of single-crystal X-ray diffraction, solid-state NMR (SSNMR), and other analytical techniques. Initial attempts to obtain a crystal structure were hampered by difficulties with twinning and problematic disorder in the final refinements. Multinuclear SSNMR analysis localized the disorder to portions of the molecule near the chiral center. As a result, single-enantiomer carvedilol phosphate was prepared and was found to crystallize in a phase that was isomorphous with the racemate, while SSNMR spectra of the single enantiomers did not contain the disorder observed in the racemate. The single-crystal X-ray structure of the (R)-enantiomer was solved and used as a starting point to successfully progress the solution of the disordered racemic crystal structure. Thermal analysis and construction of a phase diagram, along with crystallographic and spectroscopic analysis, found the crystal structure of the racemate to be a solid solution of (R)- and (S)-enantiomers, with the conformation of the molecule adjusting to fit. The crystal structures show the stoichiometry of the both the racemate and (R)-enantiomer to be a hemihydrate. The phase isomorphically dehydrates below relative humidity values of 1% and above temperatures of 125 °C as assessed by water vapor sorption studies, powder X-ray diffraction, and SSNMR. Single-crystal diffraction detected significant changes in the unit cell dimensions as the phase dehydrated, which was related to the visual appearance of opacity in a single crystal of the (R)-enantiomer. The mechanism of water incorporation was further probed spectroscopically via exchange with deuterium, 17O-, and 18O-labeled water; the results suggest that dehydration and rehydration likely proceed via narrow tunnels in the crystal structure, combined with the formation of fissures in the crystal. 2H SSNMR experiments showed that the water does not engage in solid-state jump motion even at higher temperatures.
CONTROLLED-RELEASE FLOATING PHARMACEUTICAL COMPOSITIONS
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, (2010/12/29)
The invention relates to a pharmaceutical composition comprising a plurality of controlled-release coated microparticles each comprising a floating core, on the surface of which is deposited a layer containing at least one active principle, said layer being covered with a controlled-release coating, characterized by the fact that said floating core is composed of cellulose acetate phthalate and has an apparent density of less than or equal to 0.6 g/mL and said coated microparticles have a density of less than or equal to 0.7 g/mL.
Novel amorphous carvedilol dihydrogen phosphate
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Page/Page column 5, (2009/01/24)
The present invention refers to an amorphous of carvedilol dihydrogen phosphate, the processes to obtain it, compositions containing this compound and its use to treat hypertension, congestive heart failure and angina.
